Interferon-gamma

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Interferon, gamma
IFN.png
Interferon gamma, line representation
Identifiers
Symbol(s) IFNG; IFG; IFI
External IDs OMIM: 147570 MGI107656 Homologene55526
RNA expression pattern

PBB GE IFNG 210354 at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 3458 15978
Ensembl ENSG00000111537 ENSMUSG00000055170
Uniprot P01579 Q6TDH0
Refseq NM_000619 (mRNA)
NP_000610 (protein)
NM_008337 (mRNA)
NP_032363 (protein)
Location Chr 12: 66.83 - 66.84 Mb Chr 10: 117.84 - 117.85 Mb
Pubmed search [1] [2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]


Interferon-gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons.[1] This interferon was originally called macrophage-activating factor.

Structure of IFN-γ

The IFN-γ monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region.[2][3] This is shown in the structural models below. The α-helices in the core of the structure are numbered 1 to 6.

Line and cartoon representation of a IFN-γ monomer

The biologically active dimer is formed by anti-parallel inter-locking of the two monomers as shown below. In the cartoon model, one monomer is shown in red, the other in blue.

Line and cartoon representation of a IFN-γ dimer

The structural models shown above (see protein data bank code 1FG9) are all shortened at their C-termini by 17 amino acids. Full length IFN-γ is 143 amino acids in length, the models are 126 amino acids in length. Affinity for the glycosaminoglycan heparan sulfate resides solely within the deleted sequence of 17 amino acids.[4]

Biological activity

In contrast to interferon-α and interferon-β which can be expressed by all cells, IFN-γ is secreted by Th1 cells, Tc cells, dendritic cells and NK cells. Also known as immune interferon, IFN-γ is the only Type II interferon. It is serologically distinct from Type I interferons and it is acid-labile, while the type I variants are acid-stable.

IFN-γ has antiviral, immunoregulatory, and anti-tumour properties.[5] It alters transcription in up to 30 genes producing a variety of physiological and cellular responses. Amongst the effects are:

Activation by IFN-γ is achieved by its interaction with a heterodimeric receptor consisting of IFNGR1 & IFNGR2 (interferon gamma receptors). IFN-γ binding to the receptor activates the JAK-STAT pathway. In addition, IFN-γ activates APCs and promotes Th1 differentiation by upregulating the transcription factor T-bet.

IFN-γ is the hallmark cytokine of Th1 cells (Th2 cells produce IL-4). NK cells and CD8+ cytotoxic T cells also produce IFN-γ. IFN-γ suppresses osteoclast formation by rapidly degrading the RANK adaptor protein TRAF6 in the RANK-RANKL signaling pathway, which otherwise stimulates the production of NFκB.


Therapeutic uses

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Interferon-gamma
Systematic (IUPAC) name
Human interferon gamma-1b
Identifiers
CAS number 82115-62-6
98059-61-1
ATC code L03AB03
PubChem  ?
DrugBank BTD00017
Chemical data
Formula C761H1206N214O225S6 
Mol. mass 17145.6 g/mol
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.

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Legal status
Routes  ?

Interferons are used to treat infectious diseases and cancer.

Scientists at the University of California at Berkeley have recently discovered that Diindolylmethane (DIM), a naturally occurring compound found in Brassica vegetables, upon oral consumption, is a direct and potent activator of Interferon-Gamma production and sensitivity within the body leading the way for the study of this compound as an anti-viral, anti-bacterial and anti-cancer therapeutic. As this is a dietary compound found in edible vegetables, this has caused a lot of excitement in the immunology field. This compound has also been shown to synergize with Interferon-Gamma in the expression and potentiation of the MHC-I Complex, leading to its study as a possible adjuvant to Interferon-gamma therapeutic models.

References

  1. Gray, P. W. and Goeddel, D. V. (1982). "Structure of the human immune interferon gene". Nature 298: 859–863. doi:10.1038/298859a0.
  2. Ealick, S. E., Cook, W. J. et al. (1991). "Three-dimensional structure of recombinant human interferon-gamma". Science 252: 698–702. doi:10.1126/science.1902591.
  3. Thiel, D. J. et al. (2000). "Observation of an unexpected third receptor molecule in the crystal structure of human interferon-γ receptor complex". Structure 8 (9): 927–936. doi:10.1016/S0969-2126(00)00184-2.
  4. Vanhaverbeke, C. Simorre, J-P. et al. (2004). "NMR characterization of the interaction between the C-terminal domain of interferon-γ and heparin-derived oligosaccharides" 384: 93–99. PMID 15270718.
  5. Schroder et al. (2004). "Interferon-γ an overview of signals, mechanisms and functions". Journal of Leukocyte Biology 75: 163–189. doi:10.1189/jlb.0603252.

Further reading

  • Hall, Steven S. (1997) A Commotion in the Blood. New York, New York: Henry Holt and Company. ISBN 0-8050-5841-9
  • Information on Interferon and how it relates to hepatitis c
  • Ikeda H, Old LJ, Schreiber RD (2002). "The roles of IFN gamma in protection against tumor development and cancer immunoediting.". Cytokine Growth Factor Rev. 13 (2): 95–109. PMID 11900986.
  • Chesler DA, Reiss CS (2003). "The role of IFN-gamma in immune responses to viral infections of the central nervous system.". Cytokine Growth Factor Rev. 13 (6): 441–54. PMID 12401479.
  • Dessein A, Kouriba B, Eboumbou C, et al. (2005). "Interleukin-13 in the skin and interferon-gamma in the liver are key players in immune protection in human schistosomiasis.". Immunol. Rev. 201: 180–90. doi:10.1111/j.0105-2896.2004.00195.x. PMID 15361241.
  • Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection.". Curr. HIV Res. 3 (1): 87–94. PMID 15638726.
  • Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines.". Mini reviews in medicinal chemistry 5 (12): 1093–101. PMID 16375755.
  • Chiba H, Kojima T, Osanai M, Sawada N (2006). "The significance of interferon-gamma-triggered internalization of tight-junction proteins in inflammatory bowel disease.". Sci. STKE 2006 (316): pe1. doi:10.1126/stke.3162006pe1. PMID 16391178.
  • Tellides G, Pober JS (2007). "Interferon-gamma axis in graft arteriosclerosis.". Circ. Res. 100 (5): 622–32. doi:10.1161/01.RES.0000258861.72279.29. PMID 17363708.
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